Phase II Prospective Randomized Trial of a Low-Fat Diet with Fish Oil Supplementation in Men Undergoing Radical Prostatectomy

Abstract

Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control western diet (omega-6:omega-3 ratio of 15:1) for 4–6 weeks prior to surgery. The primary endpoint was change in serum IGF-1 between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E-2 levels, omega-6:omega-3 fatty acid ratios, COX-2 and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil vs. western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki67 index), and reduced proliferation in an ex-vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, 4–6 weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology.

Prostatic and Dietary Omega-3 Fatty Acids and Prostate Cancer Progression during Active Surveillance

“…Although the analysis of patients consuming supplements has greater potential for bias (which is why we excluded them from the main analysis), it does support the protective effect of EPA in the target tissue (prostate). It has already been shown that w-3 fatty acid supplementation increases the w-3 fatty acid content of prostate tissue in specimens of prostatectomy (41,42). These observations combined with our new results suggest a potential protective effect of w-3 fatty acid supplements on prostate cancer carcinogenesis.…”

Effects ofω-3 Fatty Acids and Catechins on Fatty Acid Synthase in the Prostate: A Randomized Controlled Trial

“…Our result on green tea effect is consistent with a clinical trial of ninety-three men who completed the intervention of 6 cups/day brewed green and black tea prior to prostatectomy, which showed no significant effect of tea consumption on Ki-67 level in prostatectomy tissues (49). However, our non-significant finding of fish oil supplementation is not consistent with a clinical trial of low-fat diet with fish oil supplementation among men undergoing radical prostatectomy, which showed a significant decreased tumor tissue Ki-67 level (45) in the intervention group. This suggests that should the alteration of FAS expression slow prostate cancer development or progression it may not function by altering cell proliferation in non-malignant tissue.…”

“…Compared to an Italian study which showed a significant chemoprevention effect of green tea catechins (GTC) on prostate cancer (44), our study’s intervention doses (EGCG 600mg) were similar to the GTC study (600 mg); but our intervention period (12–20 weeks) was much short than the GTC study (1 year). Compared to a clinical trial showing a 4–6 week low-fat diet with fish oil supplementation (1g EPA+ 1.8g DHA) intervention could significantly decrease prostate tissue Ki-67 level (45), our fish oil doses (1.9g EPA+DHA) were lower. The shorter duration or lower doses may restrict our ability to discern an effect of supplementation on FAS or Ki-67 expression, especially if the variation in FAS or Ki-67 protein expression caused by fish oil or green tea supplementation is a cumulative effect.…”

ω-3 fatty acid differentially modulated serum levels of IGF1 and IGFBP3 in men with CVD: A randomized, double-blind placebo-controlled study

“…This might be probably due to the higher baseline serum IGF1 levels in prostate cancer patients unlike CVD patients participated in the present study [15,16]. Burned patients on the other hand showed a better recovery of decreased serum IGF1 levels after fish oil supplementation.…”